It is proposed to continue the analysis of the mechanisms and metabolic controls involved in the generation of currents and electrical potentials by the mammalian photoreceptor cell in darkness and in light, which may have important bearing on degenerative processes and other abnormalities of the retina. This research proposal is an experimental investigation into the sources of photoreceptor dark current in relation to the sodium gradient and the sodium-potassium pump in different functional states. Simultaneous measurements will be made of electrical and metabolic activities of isolated mammalian retinas with respect to changes in the concentrations of sodium, potassium, calcium and bicarbonate and different levels of oxygen and glucose availability and sodium-potassium pumping. Suitable procedures will be employed to restrict these responses to the photoreceptor cell layer of the isolated retinas. Metabolic parameters to be studied include aerobic and anaerobic glycolysis, oxygen consumption, retinal ATP concentrations, ATPase activities and cation transport into and out of the retina. Electrical activities, transretinal potentials and the distribution causes of the deleterious effects on photoreceptor function of glucose after inhibition of glycolysis, ouabain, and lithium will be studied. In addition, the roles of cyclic nucleotides and glutathione in metabolic and electrical activities of the photoreceptor cell will be determined. The role of potassium in the generation of glial cell currents (Slow PIII) and the c-wave of the pigment epithelium will be studied by ionic replacement studies and by the use of ion-specific microelectrodes. The experiments will be performed on isolated retinas from rat and rabbit.